Neisseria meningitidis is a bacterial pathogen that causes septicemia and meningitis. It enters the bloodstream from the nasopharynx and from there crosses the blood brain barrier to cause inflammation of the meninges. Before the organism reaches the central nervous system, it would have encountered numerous phagocytic cells, such as monocytes and macrophages. Dr. Waldbeser proposes to study the meningococcal-macrophage interaction. Bacterial outer membrane proteins play a part in this interaction. The porin PorA is known to be capable of insertion into mammalian membranes, and is known to alter phagocyte functions. The immediate goal is to clone the porA gene and to generate knockout mutants. Dr. Waldbeser proposes to study the effects of bacteria expressing different PorA levels on macrophage viability and cytokine synthesis, as well as on bacterial survival within the phagocytes. The long term goal is to study the effect of PorA on the interactions at a molecular level. In the long range projects, Dr. Waldbeser would study the effect of purified PorA on the signal transduction systems, the phagocytic function and the secretory functions of monocytes and macrophages